Fine chemical

The class of fine chemicals is subdivided either on the basis of the added value (building blocks, advanced intermediates or active ingredients), or the type of business transaction, namely standard or exclusive products.

An example in case is F.I.S., Italy, which partnered with Roche, Switzerland for custom manufacturing precursors of the benzodiazepine class of tranquilizers, such as Librium (chlordiazepoxide HCl) and Valium (diazepam).

Thus, β-lactams are structural elements of penicillin and cephalosporin antibiotics, imidazoles are found both in modern herbicides, e.g. Arsenal (imazapyr) and pharmaceuticals, e.g. the antiulcerants Tagamet (cimetidine.

A vast array of pharmaceuticals and agrochemicals are based on pyrimidines, such as Vitamin B1 (thiamine), the sulfonamide antibiotics, e.g. Madribon (sulfadimethoxime) and –half a century later– the sulfonyl urea herbicides, e.g. Eagle (amidosulfuron) and Londax (bensulfuron-methyl).

Optically active cyanohydrins, cyclopolymerization, ionic liquids, nitrones, oligonucletides, peptide (both liquid- and solid-phase), electrochemical reactions (e.g., perfluorination) and steroid synthesis are promoted by only a limited number of companies.

Large volume (> 103 mtpa) processes using chiral catalysts include the manufacture of the perfume ingredient l-Menthol and Syngenta's Dual (metolachlor) as well as BASF's Outlook (dimethenamid-P) herbicides.

Whereas the overall demand for outsourced pharmaceutical fine chemicals is expected to increase moderately (see Chapter 8), the estimated annual growth rates for the above-mentioned niche technologies are much higher.

The main categories are Oxidoreductases, Transferases, Hydrolases, Lipases (subcategory), Lyases, Isomerases and Ligases, Companies specializing in making enzymes are Novozymes, Danisco (Genencor).

The enzyme systems triggered in the particular microorganism strain lead to the excretion of the desired product into the medium, or, in the case of HMW peptides and proteins, to the accumulation within so-called inclusion bodies in the cells.

Modern isolation and membrane technologies, like reverse osmosis, ultra- and nano-filtration, or affinity chromatography can help to remove salts and by-products, and to concentrate the solution efficiently and in an environmentally friendly manner under mild conditions.

Mammalian cell culture fermentation, on the other hand, should be considered only by large fine chemical companies with a full war chest and a long-term strategic orientation.

Characteristics are high asset intensity, batch production in campaigns in multipurpose plants, above-industry-average R&D expenditures and close, multi-level and multi-functional relationships with industrial customers.

2000 – 3000 fine chemical companies exist globally, extending from small, "garage-type" outfits in China making just one product, all the way to the big, diversified enterprises, resp.

Contrary to manufacturing companies, invoicing of CROs is not based on unit product price, but on full-time equivalents (FTEs), that is, the cost of a scientist working one year on a given customer assignment.

Thus, the sales of the top tier firms, Charles River Laboratories, Fortrea, Parexel, PPD, Quintiles Transnational, all USA, and TCG Lifescience, India; are in the $1–$2 billion range, whereas the largest product CROs have revenues of a few 100 million dollars.

Provisions have to be made for a periodic examination of all acquired research results to safeguard Intellectual Property Rights (IPR) and to determine whether patent applications are indicated.

Particularities of laboratory processes that have to be eliminated include the use of large numbers of unit operations, dilute reaction mixtures, vast quantities of solvents for extraction, evaporation to dryness, drying of solutions with hygroscopic salts.

Although modern reaction calorimeters consent to foresee the effects of these different conditions to a certain extent, a direct transfer of a process from the laboratory to the industrial scale is not recommended, because of the inherent safety, environmental, and economic risks.

The necessary data have to be generated to enable the engineering department to plan the modifications of the industrial-scale plant and in order to calculate production costs for the expected large-volume requirements.

Specific provisions are the increase of overall yield, the reduction of the number of steps, raw material cost, solvent, catalyst, enzyme consumption, environmental impact.

Its main constituents are (1) reaction scheme, (2) target of project & deliverables (product, quantity, required dates, specifications), (3) list of analytical methods, (4) process development opportunities (stepwise assessment), (5) list of required reports, (6) Safety, Health and Environment (SHE) issues, (7) materials to be supplied by customer and (8) packaging & shipping information The technical part of a project usually determines its duration.

Depending on the quality of the information contained in the "technology package" received from the customer and the complexity of the project as such, particularly the number of steps that have to be performed; it can be any time between 12 and 24 months.

As the leading specialty chemical companies, Akzo Nobel, Dow, DuPont, Evonik, Chemtura and Mitsubishi are backward-integrated, the share of in-house production is estimated at 75%, leaving a merchant market of approximately $5 billion.

The active ingredients extend from high-price / low-volume fine chemicals, used for liquid crystal displays to large-volume / low-price amino acids used as feed additives.

*fine chemicals merchant market size, growth potential Examples of applications in eight areas, ranging from adhesives to specialty polymers, are listed in Table 8.

Further disadvantages are the backward integration of the big players, e.g. Akzo-Nobel, Netherlands; Ajinomoto, Japan; Danone, France; Everlight Chemical Industrial Corp., Taiwan; Evonik-Degussa, Germany; Givaudan and Nestlé, Switzerland, Novozymes, Denmark, Procter & Gamble, and Unilever USA.

After the end of the "irrational exuberance" in 2000, the industry suffered a first bust in 2003, as a result of capacity expansions, the advent of Asian competitors and a ruinous M&A activity, several billion dollars of shareholder value were destroyed.

The most recent –minor- boom is associated with stockpiling of GlaxoSmithKline's Relenza (zanamivir) and Roche's Tamiflu (oseltamivir phosphate) by many countries in order to prepare for a possible avian flu epidemic.

[citation needed] In the synthesis of small molecule fine chemicals, the use of biocatalysts and microbial fermentation enable both a more sustainable and economic production than conventional organic chemistry.

As a consequence of the harsh business climate, many Western fine chemical companies or divisions created during the "irrational exuberance" at the end of the 20th century already have exited from the sector.

Definition of Fine Chemicals (as opposed to Commodities and Specialties)
The beginning: supply contract between Smith Kline French and Lonza for cimetidine precursors
Chemical Structure of Diovan (valsartan)
Chemical / Enzymatic Synthesis of Crestor (rosuvastatin)